What is Fabry Disease?

Fabry disease is a rare inherited disorder caused by mutations in the GLA gene, which leads to deficiency of the enzyme alpha-galactosidase A. This enzyme deficiency causes a progressive buildup of globotriaosylceramide (GL-3) and other related substances in cells throughout the body.

The condition belongs to a group of disorders known as lysosomal storage diseases. Since the GLA gene is located on the X chromosome, Fabry disease primarily affects males, though females can experience varying degrees of symptoms as well. The disease manifests differently among individuals, with some experiencing severe symptoms early in life while others may have milder forms that remain undiagnosed until adulthood.

Symptoms and Diagnostic Journey

Fabry disease symptoms typically begin in childhood or adolescence. Early signs often include burning pain in hands and feet (acroparesthesia), decreased ability to sweat, distinctive skin rashes (angiokeratomas), gastrointestinal issues, and corneal whorls visible during eye examinations.

As the disease progresses, more serious complications can develop including kidney dysfunction, heart problems (enlarged heart, valve irregularities, arrhythmias), and increased risk of stroke. Diagnosis often involves measuring alpha-galactosidase A enzyme activity in blood samples, genetic testing to identify GLA gene mutations, and sometimes tissue biopsies to assess GL-3 accumulation. Unfortunately, many patients experience diagnostic delays averaging 15 years from symptom onset due to the rarity of the condition and its overlap with more common disorders.

Kidney Involvement: FSGS and Fabry

One significant manifestation of Fabry disease is its impact on kidney function. The disease can cause a condition known as focal segmental glomerulosclerosis (FSGS), which refers to scarring in parts of the kidney's filtering units (glomeruli). This is why the term "FSGS Fabry" is sometimes used when discussing kidney manifestations of the disease.

Progressive kidney damage can lead to proteinuria (protein in urine), reduced kidney function, and eventually end-stage renal disease requiring dialysis or transplantation if left untreated. Regular monitoring of kidney function through blood and urine tests is essential for patients with Fabry disease. Early intervention with appropriate treatments can help slow kidney damage progression and preserve function longer.

Treatment Provider Comparison

Several pharmaceutical companies offer enzyme replacement therapy (ERT) options for Fabry disease management. Sanofi produces Fabrazyme (agalsidase beta), while Takeda (which acquired Shire) manufactures Replagal (agalsidase alfa) - though Replagal is not currently FDA-approved in the United States.

Another treatment approach involves chaperone therapy, with Amicus Therapeutics offering Galafold (migalastat) for specific GLA mutations. This oral medication helps stabilize the patient's own enzyme.

Treatment selection depends on several factors including specific genetic mutation, disease severity, organ involvement, and regional availability. The table below provides a comparison of main treatment options:

  • Fabrazyme (Sanofi): Intravenous infusion every two weeks; suitable for all patients; extensive long-term data available
  • Replagal (Takeda): Intravenous infusion every two weeks; shorter infusion time; not available in US market
  • Galafold (Amicus): Oral capsule taken every other day; only effective for specific mutations (30-50% of patients); more convenient administration

Managing Fabry Disease Long-term

Beyond specific treatments targeting enzyme replacement or enhancement, comprehensive management of Fabry disease requires a multidisciplinary approach. Patients typically benefit from coordinated care involving nephrologists, cardiologists, neurologists, geneticists, and other specialists.

Symptomatic treatments are also important aspects of care. These may include medications for neuropathic pain, antihypertensives for blood pressure control, and antiproteinuric agents to reduce protein in urine. Pfizer and Merck manufacture several medications commonly used to manage symptoms and complications.

Genetic counseling from providers like Invitae is crucial for families affected by Fabry disease. Testing can identify carriers and affected family members who might benefit from early intervention. Patient support organizations such as National Fabry Disease Foundation provide valuable resources, community connections, and advocacy assistance.

Conclusion

Living with Fabry disease presents numerous challenges, but advances in treatment options have significantly improved outcomes for patients. Early diagnosis remains critical for preventing irreversible organ damage. The evolving landscape of therapies—from enzyme replacement to oral chaperones and emerging gene therapies—offers hope for better symptom management and disease modification.

Patients should work closely with specialists experienced in Fabry disease management to develop personalized treatment plans addressing their specific symptoms and complications. With appropriate medical care, lifestyle adjustments, and support resources, many individuals with Fabry disease can maintain good quality of life despite this chronic condition. As research continues, there's optimism for additional treatment breakthroughs that may further transform the management of this complex disorder.

Citations

This content was written by AI and reviewed by a human for quality and compliance.